LAUSR

Abstract The 1.4 MB deletion in the 17q12 region causes a contiguous gene syndrome, which was recently named 17q12 Deletion Syndrome. This region encompasses the Hepatocyte Nuclear Factor 1ß gene (HNF1ß), which plays an important role in the formation of kidneys, pancreas, liver, brain and genital tract. The deletion of HNF1ß causes variable manifestations including dysplastic or cystic renal disease, MODY 5, pancreatic and urogenital malformations, hepatopathy, and neurological disorders. MODY 5 has been described in about 80% of the patients with this deletion, but less than 5% of patients are diagnosed before 10 years of age. We herein present two patients with MODY 5 due to the deletion of 17q12 whose hyperglycemia developed within 3 years of age. The first patient was diagnosed with multi-cystic dysplastic kidneys and urogenital malformations soon after birth. Microarray, obtained as part of the investigations to determine a genetic cause, revealed a heterozygous microdeletion of 17q12 region which includes HNF1ß gene region. At three years of age, his random glucose was abnormal (204 mg/dl) and HgbA1C was then obtained. The result indicated abnormal HgbA1C level of 6.6%. Pancreatic autoantibodies, GAD65, IA-2 and Insulin autoantibodies, were negative. His fasting C-peptide was also normal (2.37 ng/ml), and diagnosis of MODY 5 was than given. He currently has chronic kidney disease stage 5. However, his HgbA1C normalized (5.5%) with diet management alone. The second patient presented at 18 months of age with hyperglycemia, which was discovered during his acute respiratory illness. HgbA1C was elevated (6.2%), and the subsequent repeat tests showed similar results. He has also a global developmental delay, and was evaluated by a neurologist who requested a microarray to determine a genetic cause of his developmental delay. The result showed a heterozygous microdeletion in the similar region encompassing HNF1ß gene. Pancreatic autoantibodies were negative.Renal ultrasound was obtained to determine the presence of renal malformations, and the result indicated bilateral dysplastic kidneys. However, his renal function remains normal to date. Even though his HgbA1C was still below the diabetic cutoff point, the combinations of hyperglycemia, dysplastic kidneys and developmental delay were consistent with 17q12 Deletion Syndrome. His HgbA1C also normalized with diet management. Our report, to the best of our knowledge, presents the earliest manifestation of abnormal glucose homeostasis in patients with HNF1ß gene deletion. We, henceforth, suggest that the screening of hyperglycemia be done in pediatric patients with cystic dysplastic kidneys to aid the timely diagnosis of MODY5.